Evidence map›Paper›PMID 31738412›Full record

ArticleCardiovascular research2020

STAT3-miR-17/20 signalling axis plays a critical role in attenuating myocardial infarction following rapamycin treatment in diabetic mice.

Arun Samidurai, Sean K Roh, Meeta Prakash, David Durrant, Fadi N Salloum, Rakesh C Kukreja, Anindita Das

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 26 citations in OpenAlex.

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  12. Integrated bioinformatics andFrontiers in nutrition · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Arun SamiduraiDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
Sean K RohDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
Meeta PrakashDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
David DurrantDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
Fadi N SalloumDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
Rakesh C KukrejaDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
Anindita DasDivision of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA.
Virginia Commonwealth University · US

Funding

Cardioprotection with mTOR InhibitionR01HL134366 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DAS, ANINDITA, KUKREJA, RAKESH C · 2016 to 2019
$2.1M
Hydrogen Sulfide for Prevention and Treatment of Ischemic Heart FailureR01HL133167 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SALLOUM, FADI N · 2016 to 2020
$1.9M
Relaxin Signaling in Post-MI Cardiac Inflammation, Adverse Remodeling and FailureR01HL142281 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SALLOUM, FADI N · 2018 to 2020
$1.2M
NHLBI NIH HHS R01 HL133167NHLBI NIH HHS R01 HL134366NHLBI NIH HHS R01 HL142281
6 · The paper itself

Abstract

aimsDeregulation of mTOR (mammalian target of rapamycin) signalling occurs in diabetes, which exacerbates injury following myocardial infarction (MI). We therefore investigated the infarct-limiting effect of chronic treatment with rapamycin (RAPA, mTOR inhibitor) in diabetic mice following myocardial ischaemia/reperfusion (I/R) injury and delineated the potential protective mechanism. METHODS AND

resultsAdult male diabetic (db/db) or wild-type (WT) (C57) mice were treated with RAPA (0.25 mg/kg/day, intraperitoneal) or vehicle (5% DMSO) for 28 days. The hearts from treated mice were subjected to global I/R in Langendorff mode. Cardiomyocytes, isolated from treated mice, were subjected to simulated ischaemia/reoxygenation (SI/RO) to assess necrosis and apoptosis. Myocardial infarct size was increased in diabetic heart following I/R as compared to WT. Likewise, enhanced necrosis and apoptosis were observed in isolated cardiomyocytes of diabetic mice following SI/RO. Treatment with RAPA reduced infarct size as well as cardiomyocyte necrosis and apoptosis of diabetes and WT mice. RAPA increased STAT3 phosphorylation and miRNA-17/20a expression in diabetic hearts. In addition, RAPA restored AKT phosphorylation (target of mTORC2) but suppressed S6 phosphorylation (target of mTORC1) following I/R injury. RAPA-induced cardioprotection against I/R injury as well as the induction of miR-17/20a and AKT phosphorylation were abolished in cardiac-specific STAT3-deficient diabetic mice, without alteration of S6 phosphorylation. The infarct-limiting effect of RAPA was obliterated in cardiac-specific miRNA-17-92-deficient diabetic mice. The post-I/R restoration of phosphorylation of STAT3 and AKT with RAPA were also abolished in miRNA-17-92-deficient diabetic mice. Additionally, RAPA suppressed the pro-apoptotic prolyl hydroxylase (Egln3/PHD3), a target of miRNA-17/20a in diabetic hearts, which was abrogated in miRNA-17-92-deficient diabetic mice.

conclusionInduction of STAT3-miRNA-17-92 signalling axis plays a critical role in attenuating MI in RAPA-treated diabetic mice. Our study indicates that chronic treatment with RAPA might be a promising pharmacological intervention for attenuating MI and improving prognosis in diabetic patients.

Indexed as

AnimalsApoptosisDiabetes MellitusDisease Models, AnimalIsolated Heart PreparationMaleMice, Inbred C57BLMice, KnockoutMicroRNAsMyocardial InfarctionMyocardial Reperfusion InjuryMyocytes, CardiacNecrosisPhosphorylationProto-Oncogene Proteins c-aktSignal TransductionMicroRNAsMIRN17-92 microRNA, mouseMirn17 microRNA, mouseMirn20 microRNA, mousemTOR protein, mouseProto-Oncogene Proteins c-aktSirolimusStat3 protein, mouseSTAT3 Transcription FactorTOR Serine-Threonine KinasesApoptosisDiabetesEgln3/PHD3Ischaemia/reperfusionmiR-17-92mTORSTAT3

Identifiers

PMID31738412
PMCPMC8463091
OpenAlexW2986719693

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.